This research proposal deals with the process of excitation and excitation-contraction coupling in heart muscle. The experimental work is divided into four major categories. 1. Comparative E-C coupling in mammalian heart. The object of this study is to gain some information regarding the function of SR in in vivo heart. The time, voltage, frequency, ionic and drug dependence of contraction and I Ca under voltage clamp conditions will be compared in selected mammalian species and in neonatal cat hearts. Sterological studies will be carried out to correlate the physiological data with ultrastructural variations. 2) Calcium transport mechanism in the frog heart. The object of this study is to determine the contribution of I Ca, Na-Ca, and the K-C transport systems to the activation of contraction. K ion and Ca ion 2 electrodes will be used in combination with voltage clamp technique to quantify the magnitude of ionic fluxes and the stoichiometry of the coupled transport system. Divalent cations and organic agents will be used to determine the requirement of the calcium transport system. 3. Mechanism of the plateau in mammalian heart. This study is based on recent findings that gm during the plateau in the frog heart is constant. The "chopped" voltage clamp technique in combination with the "guard gap" procedure will be used to determine: a) if gm of mammalian plateau is constant; b) the temperature, ionic and drug dependence of gm. 4. Ca ion 2 and K ion fluxes during activity. The object of this study is to determine the frequency and ionic dependence of Na ion pump in intact myocardium. K ion micron-electrodes placed in the extracellular space will be used to monitor the time course of accumulation and depletion of K ion with activity. Experiments using Ca-electrodes will involve a) construction of the electrode; b) determination of the magnitude and the time course of calcium depletion from extracellular space during activity.